The present invention relates to newly identified calpain, Rt88 protein, which has been of the retina in eye tissues, and a DNA encoding it.
Calpain is present, in particular, in the cytoplasm of animal cells and is a cysteine protease which is activated by calcium. Several molecular species have been known in calpain. For analyzing the structure, their cDNA""s have been cloned and, at present, the presence of xcexc-and m-calpain which are generally expressed in various tissues, as well as tissue-specific calpain such as, for example, p94 which is specifically expressed in a skeleton muscle is revealed [Seikagaku (Biochemistry), Vol. 65, No. 7, pp. 537-552 (1993); Jikken Igaku (Experimental Medicine), Vol. 13, No. 9, pp. 35-42 (1995)].
Although details of physiological functions of calpain are not yet elucidated, calpain has been considered to have functions of a calcium receptor in cells and to be concerned in, for example, signal transduction, control of transcription, propagation and differentiation of cells, and the like.
Recently, it has been reported that a mutant gene of calpain p94 specifically expressed in a skeleton muscle is one of causative genes of a kind of dystrophy, myodystropy, which is known to be a disease wherein differentiated cells fall into spontaneous degeneration or atrophy without any anticipation disorder such as inflammation or injury (Isabelle Richard et al., Cell, 81, 28-40 (1995)). In addition, it has been found that p94 protein is decreased in myodystrophy (Melissa J. Spencer et al., Journal of the Neurological Science, 146, 173-178 (1997)).
On the other hand, in general, retinal degenerative diseases are divided into dystrophy and other degenerative diseases. Dystrophy is hereditary and, in many cases, the prognosis of vision is pessimistic. Then, dystrophy is of importance from clinical viewpoint (Yoshihiro Hotta, xe2x80x9cThe Cause of Retinal Degenerationxe2x80x9d in Atarashii Ganka (Journal of the Eye), 13 (7): 993-1001, 1996). In particular, at present, pigmentary retinal degeneration is designated as an objective disease in the Ministry of Health and Welfare Research Work for Treatment of Specific Diseases.
However, no study of the relation between dystrophy and calpain in retinal degenerative diseases has been found heretofore in the prior art.
The main object of the present invention is to investigate calpain which is tissue-specifically expressed in the retina of eye tissues, to isolate its gene, to determine the structure of a protein and to use them in studies of diseases in ophthalmologic field and in treatment and prevention of diseases in ophthalmologic field, in particular, retinal degenerative diseases.
This object as well as other objects and advantages of the present invention will become apparent to those skilled in the art with reference to the attached drawings.